Abstract

Purpose:Abnormal DNA methylation is associated with many human cancers. The aim of the present study was to identify novel methylation markers in prostate cancer (PCa) using microarray analysis, and to test whether those markers could discriminate normal and PCa cells.
Experimental Design:Microarray-based DNA methylation and gene expression profiling was carried out using a panel of PCa cell lines and a control normal prostate cell line. The methylation status of candidate genes in prostate cell lines was confirmed by real-time reverse transcriptase polymerase chain reaction, bisulfite sequencing analysis and treatment with a demethylation agent. DNA methylation and gene expression analysis in 203 human prostate specimens including 106 PCa and 97 benign prostate hyperplasia (BPH) was performed. Further validation using microarray gene expression data from the Gene Expression Omnibus (GEO) was also carried out.
Results:Epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was identified as a lead candidate methylation marker for PCa. The gene expression level of EFEMP1 was significantly higher in tissue samples from patients with BPH as compared to PCa (P < 0.001). The sensitivity and specificity of EFEMP1 methylation status in discriminating between PCa and BPH reached 95.3% (101/106) and 86.6% (84/97), respectively. From the GEO data set, we confirmed that the expression level of EFEMP1 was significantly different between PCa and BPH.
Conclusions:Genome-wide characterization of DNA methylation profiles enabled the identification of EFEMP1 aberrant methylation patterns in PCa. EFEMP1 might be a useful indicator for the detection of PCa.